1. Field of he Invention
The present invention relates to a novel inhibitor of protein synthesis and also to methods for its isolation, its use and pharmaceutical compositions in which it is present.
2. Background Information
Proteins which inhibit protein synthesis in eucaryotic systems have been found in the seeds or other parts of a number of plants. Among these proteins, ricin, abrin and modecin inhibit protein synthesis in both cellular systems and acellular systems and are therefore highly toxic to animals. By contrast, other proteins, which are effective only on acellular systems, have a low or zero toxicity to animals, perhaps because they cannot enter the cells.
In general, these proteins irreversibly inactivate the ribosomal subunit 60 S, which is then incapable of reacting with the elongation factor 2. Consequently, they are of interest in the study of protein synthesis and it has also been proposed to use them for combating tumors.
A protein of this type will be denoted hereafter by the term "ribosome-inactivating protein" (RIP). The best-known RIP is ricin, which is obtained by extracting the seeds of the castor-oil plant. Another RIP, gelonin, has recently been described and a review on RIP's has been published in FEBS Letters, 1986, 195 (1,2), pages 1-8.
A protein extracted from the roots of Trichosanthes kirilowii--trichosanthin--has recently been described (Nature, 1986, 321, 477-478) whose sequence is homologous to a certain degree with the subunit A of ricin D.
It has now been found that a novel and exceptionally powerful RIP which is different from trichosanthin can be extracted from the seeds of Trichosanthes kirilowii. This novel RIP will hereafter be referred to as "trichokirin".